The overall objective of this K01 proposal is to enable Dr. Friedman to develop the skills and expertise necessary for independent integrative research on psychosocial well-being and health in aging adults. Inflammation typically increases with age and has been linked to a range of age-related disorders, including heart disease and diabetes. The key hypothesis of the proposed research is that positive psychosocial functioning will predict lower levels of blood-borne inflammatory proteins in older adults and will moderate the negative impact of chronic life adversity. In order to conduct this work, Dr. Friedman seeks additional training in geriatric health, epidemiology, and analytical methodology. The proposed Training Plan includes both formal coursework and intensive mentorship focused on these topics. These didactic activities will complement Dr. Friedman's background in psychoneuroimmunology and enable him (a) to examine multiple dimensions of human functioning using longitudinal psychosocial data from the Survey of Midlife in the United States (MIDUS) and (b) to link these data to newly assessed neurobiological measures, including inflammatory factors. The Research Plan will utilize the new concepts and techniques learned to test four key hypotheses: (1) positive psychosocial functioning will predict low levels of inflammatory proteins and will moderate the associations of inflammation with low socioeconomic status and chronic stress; (2) neuroendocrine function (diurnal cortisol slopes; cortisol levels under resting conditions and in response to laboratory stressors) will mediate the association of psychosocial functioning and inflammatory proteins; (3) neural indices of emotion regulation (EEG asymmetry) will predict low levels of inflammatory proteins; and (4) integrative analyses of psychosocial, sociodemographic, neuroendocrine, and neural circuitry factors will identify pathways through which these multiple domains interact (using recursive partitioning) to predict high or low levels of inflammatory proteins. This combination of didactic and research experiences will equip Dr. Friedman with the knowledge and skills necessary for a successful career transition to independent research focused on multi-domain human experience and health. The research is also expected to generate new information about links between positive psychosocial functioning and inflammatory processes that will aid in the identification and targeting of effective interventions to improve health and well-being in later life. [unreadable] [unreadable] [unreadable] [unreadable]